Expression of Carbonic Anhydrase IX Correlates with Histologic Grade and Metastasis in Osteosarcoma
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Background : Carbonic anhydrase IX (CA9) is reportedly overexpressed in several types of carcinomas, but little is known about the expression pattern of CA9 in osteosarcoma. We aimed to assess the prevalence of CA9 expression and its prognostic implications in osteosarcoma patients. Methods : We compared immunohistochemical expression of CA9 between conventional, high-grade and low-grade, central osteosarcomas. Specimens were obtained before chemotherapy and stained with anti-human CA9 antibody. We also evaluated the histologic grade, presence of metastasis, and patient prognosis. Results : Among 38 samples of conventional high-grade osteosarcoma, 22 (57.9%) tumors displayed CA9 overexpression. Twenty-five cases of low-grade central osteosarcomas were all negative (p < 0.0001). CA9 expression was significantly associated with the presence of metastasis (p = 0.0010). The overall survival rate was significantly reduced with increased CA9 expression (p = 0.0012), higher histologic grade (p < 0.0001), and younger age (p = 0.0140). However, the overall survival rate was not significantly correlated with gender, tumor size, or American Joint Committee on Cancer stage. Conclusions : CA9 expression is a frequent and tumor-specific event in osteosarcoma. CA9 expression is associated with higher grade tumors, metastasis and poor prognosis for the osteosarcoma patients.
Abstract
Background : Carbonic anhydrase IX (CA9) is reportedly overexpressed in several types of carcinomas, but little is known about the expression pattern of CA9 in osteosarcoma. We aimed to assess the prevalence of CA9 expression and its prognostic implications in osteosarcoma patients. Methods : We compared immunohistochemical expression of CA9 between conventional, high-grade and low-grade, central osteosarcomas. Specimens were obtained before chemotherapy and stained with anti-human CA9 antibody. We also evaluated the histologic grade, presence of metastasis, and patient prognosis. Results : Among 38 samples of conventional high-grade osteosarcoma, 22 (57.9%) tumors displayed CA9 overexpression. Twenty-five cases of low-grade central osteosarcomas were all negative (p < 0.0001). CA9 expression was significantly associated with the presence of metastasis (p = 0.0010). The overall survival rate was significantly reduced with increased CA9 expression (p = 0.0012), higher histologic grade (p < 0.0001), and younger age (p = 0.0140). However, the overall survival rate was not significantly correlated with gender, tumor size, or American Joint Committee on Cancer stage. Conclusions : CA9 expression is a frequent and tumor-specific event in osteosarcoma. CA9 expression is associated with higher grade tumors, metastasis and poor prognosis for the osteosarcoma patients.
참고문헌 (27)
- Harris AL, "Hypoxia:a key regulatory factor in tumour growth", Nat Rev Cancer, 2, pp.38~47 (2002)
- Subarsky P, "The hypoxic tumour microenvironment and metastatic progression", Clin Exp Metastasis, 20, pp.237~250 (2003)
- Giatromanolaki A, "Expression of hypoxia-inducible carbonic anhydrase-9 relates to angiogenic pathways and independently to poor outcome in non-small cell lung cancer", Cancer Res, 61, pp.7992~7998 (2001)
- Loncaster JA, "Carbonic anhydrase(CA IX)expression,a potential new intrinsic marker of hypoxia:correlations with tumor oxygen measurements and prognosis in locally advanced carcinoma of the cervix", Cancer Res, 61, pp.6394~6399 (2001)
- Ivanov S, "Expression of hypoxia-inducible cell-surface transmembrane carbonic anhydrases in human cancer", Am J Pathol, 158, pp.905~919 (2001)
- Koukourakis MI, "Hypoxia-regulated carbonic anhydrase-9(CA9)relates to poor vascularization and resistance of squamous cell head and neck cancer to chemoradiotherapy", Clin Cancer Res, 7, pp.3399~3403 (2001)
- Hedley D, "Carbonic anhydrase IX expression,hypoxia,and prognosis in patients with uterine cervical carcinomas", Clin Cancer Res, 9, pp.5666~5674 (2003)
- Bui MH, "Carbonic anhydrase IX is an independent predictor of survival in advanced renal clear cell carcinoma:implications for prognosis and therapy", Clin Cancer Res, 9, pp.802~811 (2003)
- Supuran CT, "Carbonic anhydrase inhibitors", Med Res Rev, 23, pp.146~189 (2003)
- Ma*seide K, "Carbonic anhydrase IX as a marker for poor prognosis in soft tissue sarcoma", Clin Cancer Res, 10, pp.4464~4471 (2004)
- Unni KK, "Grading of bone tumors", Semin Diagn Pathol, 1, pp.165~172 (1984)
- Opavsky@ R, "Human MN", CA9 gene,a novel member of the carbonic anhydrase family:structure and exon to protein domain relationships, 1996, pp.33, 480~487
- Ivanov SV, "Down-regulation of transmembrane carbonic anhydrases in renal cell carcinoma cell lines by wildtype von Hippel-Lindau transgenes", Proc Natl Acad Sci U S A, 95, pp.12596~2601 (1998)
- Pastorek J, "Cloning and characterization of MN,a human tumor-associated protein with a domain homologous to carbonic anhydrase and a putative helix-loop-helix DNA binding segment", Oncogene, 9, pp.2877~2888 (1994)
- Al-Ahmadie HA, "Carbonic anhydrase IX expression in clear cell renal cell carcinoma:an immunohistochemical study comparing 2 antibodies", Am J Surg Pathol, 32, pp.377~382 (2008)
- Turner JR, "MN antigen expression in normal,preneoplastic,and neoplastic esophagus:a clinicopathological study of a new cancer-associated biomarker", Hum Pathol, 28, pp.740~744 (1997)
- Hui EP, "Coexpression of hypoxia-inducible factors 1alpha and 2alpha,carbonic anhydrase IX,and vascular endothelial growth factor in nasopharyngeal carcinoma and relationship to survival", Clin Cancer Res, 8, pp.2595~2604 (2002)
- Crabb SJ, "Can clinically relevant prognostic subsets of breast cancer patients with four or more involved axillary lymph nodes be identified through immunohistochemical biomarkers? A tissue microarray feasibility study", Breast Cancer Res, 10, pp.R6~ (2008)
- Kyndi M, "Carbonic anhydrase IX and response to postmastectomy radiotherapy in high-risk breast cancer: a subgroup analysis of the DBCG82 b and c trials", Breast Cancer Res, 10, pp.R24~ (2008)
- Hynninen P, "Expression of transmembrane carbonic anhydrases IX and XII in ovarian tumours", Histopathology, 49, pp.594~602 (2006)
- Saarnio J, "Immunohistochemical study of colorectal tumors for expression of a novel transmembrane carbonic anhydrase,MN", CA IX,with potential value as a marker of cell proliferation, 1998, pp.153, 279~285
- Ord JJ, "An investigation into the prognostic significance of necrosis and hypoxia in high grade and invasive bladder cancer", J Urol, 178, pp.677~682 (2007)
- Ma*seide K, "Can sparsely and heterogeneously expressed proteins be detected using tissue microarrays? A simulation study of the hypoxia marker carbonic anhydrase IX(CA IX)in human soft tissue sarcoma", Pathol Res Pract, 204, pp.175~183 (2008)
- Höckel M, "Tumor hypoxia:definitions and current clinical,biologic,and molecular aspects", J Natl Cancer Inst, 93, pp.266~276 (2001)
- Bartosová M, "Expression of carbonic anhydrase IX in breast is associated with malignant tissues and is related to overexpression of c-erbB2", J Pathol, 197, pp.314~321 (2002)
- Wykoff CC, "Hypoxia-inducible expression of tumor-associated carbonic anhydrases", Cancer Res, 60, pp.7075~7083 (2000)
- Nordsmark M, "The relationship between tumor oxygenation and cell proliferation in human soft tissue sarcomas", Int J Radiat Oncol Biol Phys, 35, pp.701~708 (1996)